The prefrontal cortex (PFC) plays a critical role for behaviors that require a high level of mental integration. Damage to this structure results in an inability to select, maintain, and associate temporally disconnected stimuli. Although these dysfunctions have been attributed to disruptions in prefrontal activity and an inability to learn, they also could, however, result from a deficit in prefrontal memory storage. Our preliminary data show that in addition to the hippocampus, the medial RFC is involved in long-term memory storage for trace fear conditioning, a hippocampal-dependent associative learning paradigm. Training-related activation of extracellular signal-regulated kinase (ERK) occurred in the mPFC prior to that observed in the hippocampus, suggesting that mPFC plasticity may not depend on hippocampal information storage (or plasticity). As dopamine has been repeatedly shown to be necessary for proper prefrontal function, dopamine D1 receptor activity may modulate mPFC memory storage. Based on these observations and others, the present proposal will test the general hypothesis that information is stored long-term within the prefrontal cortex as a direct result of training in higher cognitive tasks. The three Specific Aims are: (1) To examine if molecular correlates of long-term memory occur in the mPFC as a result of trace fear conditioning (2) To examine the contribution of mPFC dopamine receptors in long-term memory for trace fear conditioning. (3) To examine the interaction between hippocampal and mPFC plasticity during memory storage for trace fear conditioning. Presently, there is an incomplete understanding of the process of memory storage. Investigation of PFC memory storage could be crucial to our understanding of this process and to the contribution of memory storage within the mPFC in guiding complex behaviors. The study will explore the role of the prefrontal cortex in long-term memory storage. As the function of the prefrontal cortex is often compromised as a result of neurological and psychiatric disorders, in aging, and following brain injury, an understanding of the role of this structure in long-term memory will provide information that will help guide treatment strategies for these conditions. [unreadable] [unreadable] [unreadable]